Immunotoxicity of Combined TBT and Co-planar PCB Exposures in Fish

EPA Grant Number: R823881
Title: Immunotoxicity of Combined TBT and Co-planar PCB Exposures in Fish
Investigators: Rice, Charles D.
Institution: Mississippi State University
Current Institution: Mississippi State University - Main Campus
EPA Project Officer: Manty, Dale
Project Period: October 1, 1995 through September 30, 1998
Project Amount: $274,120
RFA: Exploratory Research - Environmental Biology (1995) RFA Text |  Recipients Lists
Research Category: Biology/Life Sciences , Economics and Decision Sciences , Health , Ecosystems


Two of the most ubiquitous groups of industrial contaminants are halogenated aromatic hydrocarbons (HAHs) and organometals. Structure activity relationships indicate that coplanar polychlorinated biphenyls, such as 3,3',4,4'-Tetrachlorobiphenyl (PCB-77) and 3,3',4,4',5-Pentachlorobiphenyl (PCB-126), are structurally related to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic HAH. These compounds are highly immunotoxic in rodent models and may also be immunotoxic in fish. Tributyltin (TBT), a trialkylated organotin, is used primarily as an aquatic antifouling biocide in aquacultural and boating environments and, as with HAHs, has the ability to bioconcentrate and bioaccumulate in aquatic food chains. As with immunotoxic HAHs, a primary target organ of TBT toxicity is the immune system. Coplanar PCBs, such as 3,3',4,4',5-PCB, and TBT have been shown to induce thymic atrophy and T-cell related immunodeficiencies in rodents; therefore exposure to these compounds in combination may lead to general immunopathology and increased disease susceptibility at levels of each compound that alone may not be toxic. Susceptibility to coplanar PCB toxicity, at least in part, is Ah-locus related, but TBT-related toxicity is not associated with any known genetic locus. While coplanar PCBs are powerful inducers of P-4501A related enzyme activities, TBT inactivates cytochrome P-450, especially P4501A products. The observation that both PeCB and TBT induce thymic atrophy, which is an Ah-R associated phenomenon in planar PCB immunotoxicity, leads to the hypothesis that exposure to both may have synergistics effects even though different mechanisms of action are involved. Alternatively, some of the immunosuppression following exposure to co-planar PCBs may be a result of P-450 related end products (toxic metabolites, leukotrienes, prostaglandins, others...). By degrading P-450, TBT may be antagonistic to induction properties of planar PCBs thereby antagonizing some of their immunotoxic properties. Quantification of P-4501A levels and P4501A activity (EROD) following concomitant exposure to both compounds would begin to address this alternative hypothesis. This study will test the primary hypothesis that exposure to both 3,3'4,4',5-PCB and TBT will synergistically affect immune functions in channel catfish, Ictalurus punctatus, at doses that are relatively non-toxic when each is given alone. These immunological parameters will be compared to hematology, plasma chemistry, and the induction of hepatic P4501A as biomarkers of exposure and effect following combined exposure to 3,3',4,4',5-pentachlorobiphenyl and TBT. Experiments to identify cellular/molecular mechanisms of action will be initiated.

Publications and Presentations:

Publications have been submitted on this project: View all 22 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 13 journal articles for this project

Supplemental Keywords:

Health, Scientific Discipline, Waste, Ecosystem Protection/Environmental Exposure & Risk, Bioavailability, Toxicology, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Biology, organometals, immune system effects, epidemelogy, toxic metabolites, immunotoxicology, toxic environmental contaminants, bioaccumulation, cell culture, fish-borne toxicants, co-planar PCB exposures

Progress and Final Reports:

Final Report